Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.
We conducted an ...international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.
During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval CI, 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.
In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).
Summary Background Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and ...cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. Methods SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2–90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov , number NCT01994720. Findings Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 50% to ticagrelor and 6610 50% to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 95% CI 0·53–0·88; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 0·84–1·13; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group. Interpretation In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention. Funding AstraZeneca.
In the title salt, (C
2
H
8
N)
2
Ni(H
2
O)
6
)(SO
4
)
2
·2H
2
O, the Ni
II
cation is located on a centre of inversion and exhibits a slightly distorted octahedral arrangement of water molecules. The ...Ni—O bond lengths in the complex Ni(H
2
O)
6
2+
cation show a distribution as in the related Tutton salt (NH
4
)
2
Ni(H
2
O)
6
(SO
4
)
2
, but are longer in average 2.056 (13)
versus
2.037 (12) Å. The noncoordinating water molecules and dimethylammonium cations connect the sulfate and Ni(H
2
O)
6
2+
octahedra
via
O—H...O and N—H...O hydrogen bonds from weak up to medium strength into a three-dimensional framework whereby the complex metal cations and sulfate anions are arranged in sheets parallel (001).
In the title salt, (C
2
H
10
N
2
)
3
Pr
2
(SO
4
)
6
·6H
2
O, the Pr
III
cation is surrounded ninefold by five sulfate groups (two monodentate and three chelating) and by one water molecule range of ...Pr—O bond lengths 2.383 (3) to 2.582 (3) Å. The Pr(SO
4
)
5
(H
2
O) groups are arranged in sheets parallel to (010). Two crystal water molecules and two ethylenediammonium cations (one with point group symmetry -1) connect the sheets
via
O—H...O and N—H...O hydrogen bonds from weak up to medium strength into a three-dimensional framework structure.
In the title salt, (CH
3
)
2
NH
2
Cu(HSO
4
)(SO
4
)(H
2
O)
4
, one type of cation and anion is present in the asymmetric unit. The Cu
II
atom in the complex anion, Cu(HSO
4
)(SO
4
)(H
2
O)
4
−
, has ...a tetragonal bipyramidal 4 + 2 coordination caused by a Jahn–Teller distortion, with the aqua ligands in equatorial and two O atoms of tetrahedral HSO
4
and SO
4
units in apical positions. Both types of ions form sheets parallel to (010). The interconnection within and between the sheets is reinforced by O—H...O and N—H...O hydrogen bonds, respectively, involving the water molecules, the two types of sulfate anions and the ammonium groups.
In the title molecular salt, NH
2
(CH
2
CH
3
)
2
H
2
PO
4
, two unique types of cations and anions, which are configurationally very similar, are present in the asymmetric unit. Both ions form sheets ...approximately parallel to (-1-1) linked by weak hydrogen bonds. The interconnection within and between the sheets is reinforced by O—H...O and N—H...O hydrogen bonds involving the tetrahedral H
2
PO
4
anions and the ammonium groups.
Background P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual ...antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year. Study Design PEGASUS-TIMI 54 is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor in addition to aspirin (75-150 mg) for the prevention of major adverse cardiovascular events in patients with a history of myocardial infarction and risk factors. Patients with a history of spontaneous myocardial infarction within 1 to 3 years are randomized in a 1:1:1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or matching placebo, all with low dose ASA, until the end of the study. The primary endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. Recruitment began in October 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial is planned to continue until the latest of either 1,360 adjudicated primary end points are accrued or the last patient randomized has been followed for at least 12 months. Conclusions PEGASUS-TIMI 54 is investigating whether the addition of intensive antiplatelet therapy with ticagrelor to low-dose aspirin reduces major adverse cardiovascular events in high-risk patients with a history of myocardial infarction.
The title salt, (C
2
H
8
N)
2
Co(H
2
O)
6
)(SO
4
)
2
·2H
2
O, is isotypic with (C
2
H
8
N)
2
Ni(H
2
O)
6
)(SO
4
)
2
·2H
2
O. The Co—O bond lengths in the Co(H
2
O)
6
2+
complex cation show very ...similar distances as in the related Tutton salt (NH
4
)
2
Co(H
2
O)
6
)(SO
4
)
2
average 2.093 (17) Å, but are significantly longer than in the isotypic Ni
II
compound (Δ
d
≃ 0.04 Å). The cobalt cation reaches an overall bond-valence sum of 1.97 valence units. The S—O distances are nearly equal, ranging from 1.454 (4) to 1.470 (3) Å mean 1.465 (12) Å; however, the O—S—O angles vary clearly from 108.1 (2) to 110.2 (2)° average bond angle 109.5 (9)°. The non-coordinating water molecules and dimethylammonium cations connect the sulfate tetrahedra and the Co(H
2
O)
6
2+
octahedron
via
O—H...O and N—H...O hydrogen bonds of weak up to medium strength into a three-dimensional framework whereby the complex metal cations and sulfate anions are arranged in sheets parallel to (001).
Abstract Background Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has ...modest evidence supporting a reduction in cardiovascular events in patients with PAD, while clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. Study Design EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding. Recruitment began in December 2012 and completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1364 adjudicated primary end points occur. Conclusions The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.
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